Neurologic complications of HIV disease and their treatment

Abstract

Findings on the nervous system complications of HIV disease and their impact on people living with HIV continue to accumulate. New reports at the 17th Conference on Retroviruses and Opportunistic Infections this year confirmed that HIV-associated neurocognitive disorders (HAND) are common, even among effectively treated individuals. Risk of HAND correlated with nadir CD4+ cell counts and with cerebrospinal fluid (CSF) viral loads that were at least as high as plasma viral loads. Other new data regarding risk factors for HAND implicated vascular disease, apolipoprotein E and mannose binding lectin genotypes, reduced resting cerebral blood flow, and HIV mutants that cause macrophages to shed the HIV gp120 protein. Two analyses linked worse neurocognitive performance to use of efavirenz, raising concerns about neurotoxicity. Analyses comparing differences in estimated distribution of antiretroviral drugs into the central nervous system (CNS) to neurocognitive outcomes using the 2008 version of the CNS penetration-effectiveness (CPE) ranking system did not support a hypothesis of neurotoxicity but did have mixed results, some supporting a benefit and some supporting no effect. Of note, a revised version of the CPE ranking system was presented that was more strongly associated with CSF viral loads than the 2008 version. Reports also estimated that primary CSF virologic failure occurs in 3% to 10% of treated individuals, although the clinical consequences of this remain uncertain. New data on common coinfections in people with HIV identified that a specific strain of Treponema pallidum may be more neurovirulent than other strains, that hepatitis C virus Core protein may be neurotoxic, and that hepatitis B virus may replicate in the nervous system. The extensive data presented will inform new research and clinical decisions in the coming year.